The basic objective of this proposal is to construct, computerize and introduce for use in the fields of toxicology, pharmacology and fermentation biochemistry a radiogas chromatograph/mass spectrometer (RGC/MS) in which the MS module is a quadrupole instrument and is coupled in series with the counter unit. A prototype RGC/MS in which the MS module is a sector instrument and is coupled in parallel with the counter, already exists in our laboratory. As a model system with which to test the applicability of the RGC/quad-MS to the needs of the areas mentioned above, secondary metabolism in Penicillium patulum will be studied. As a model of drug metabolism the catabolism of 6-methylsalicylic acid, m-cresol, patulin, acetylacetone and dehydroacetic acid will be used; as a model of fermentation product biosynthesis, the formation of patulin will be examined; as a model for drug mode of action studies, the effect of acetylacetone and dehydroacetic acid on P. patulum primary and secondary metabolism will be probed. To test the ability of the RGC/quad-MS unit to monitor the flow of carbon through metabolic networks the pattern of carbon flow in secondary metabolite producing and non-producing states of P. patulum development will be examined. The ability of the RGC/MS to give data for which mathematic models of metabolism can be established, will be assessed wherever possible.